Dissociation between 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission computed tomography, ultrasound and clinical assessments in patients with non-severe rheumatoid arthritis, including remission.
[en] BACKGROUND: Inflammation of patients joints with severe disease activity of rheumatoid arthritis (RA) has already been visualized and quantified by 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission computed tomography ([(18)F] FDG PET/CT), but little is known about the metabolic status and its relationship with clinical and ultrasonography (US) metrology in patients with low/moderate activity or in remission. METHODS: Clinical assessments [based on 28-joint disease activity score (DAS(28)-CRP) and Clinical Disease Activity Index (CDAI)], [(18)F] FDG PET/CT, US and X-ray were performed on 63 RA patients classified into remission or low/moderate or severe disease activity groups. PET/CT was visually and then semi-quantitatively analysed by determining the standardized uptake value (SUV) of positive joints. RESULTS: Of the 1764 joints, 21.1% were tender only, 13.7% swollen only, 27.6% tender or swollen, 7.3% tender and swollen, 20.5% PET/CT-positive and 8.6% US-positive. PET and US measurements were correlated, albeit with poor concordance. The positive predictive value of PET/CT for clinical evaluation (tender and/or swollen) was low, whereas its negative predictive value was high. Highly significant differences were found with the number of PET/CT-positive joints and with cumulative SUV between "severe" and "non-severe" patients (including those in remission and those with low/moderate activity) and not between those classified as "remission" and "non-remission" or "remission" and "low/moderate activity". Moreover, the correlation between PET/CT measurements and clinical activity was positive only in the CDAI severe disease group. In patients in remission or with low/moderate activity, only 20-30% of joints were PET/CT-negative. In remission, PET/CT and US were positive in different joints, and PET/CT-positive but US-negative joints mainly exhibited RA (38.1%) or normal (49.2%) and not osteoarthritic (12.7%) X-ray patterns. CONCLUSIONS: [(18)F] FDG PET/CT was effective at distinguishing patients with severely active disease from other patients. In non-severe RA patients, including those in remission, PET/CT results are discordant from US and clinical observations. A longitudinal analysis is needed to explore the clinical relevance of such infra-clinical disease.
Disciplines :
Rheumatology
Author, co-author :
Rinkin, Charline; Centre Hospitalier Universitaire de Liège - CHU > Rhumatologie
Fosse, Pacôme; Centre Hospitalier Universitaire d'Angers - CHU ANGERS
MALAISE, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Rhumatologie
Chapelier, Nathalie; Centre Hospitalier Universitaire de Liège - CHU > Rhumatologie
Horrion, Jil; Centre Hospitalier Universitaire de Liège - CHU > Radiologie
Seidel, Laurence ; Centre Hospitalier Universitaire de Liège - CHU > SIME > Biostatistique
Albert, Adelin ; Université de Liège - ULiège > Département des sciences de la santé publique > Département des sciences de la santé publique
Hustinx, Roland ; Université de Liège - ULiège > Département des sciences cliniques > Médecine nucléaire
Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie
Language :
English
Title :
Dissociation between 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission computed tomography, ultrasound and clinical assessments in patients with non-severe rheumatoid arthritis, including remission.
Stoffer MA, Schoels MM, Smolen JS, Aletaha D, Breedveld FC, Burmester G, et al. Evidence for treating rheumatoid arthritis to target: results of a systemic literature search update. Ann Rheum Dis. 2016;75(1):16–22. 10.1136/annrheumdis-2015-207526. DOI: 10.1136/annrheumdis-2015-207526
van der Heijde D, Klareskog L, Rodriguez-Valverde V, et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis. Two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum. 2006;54:163–74.
de Punder YMR, Fransen J, Kievit W, Houtman PM, Visser H, van de Laar MAFJ, et al. The prevalence of clinical remission in RA patients treated with anti-TNF: results from the Dutch rheumatoid arthritis monitoring (DREAM) registry. Rheumatol. 2012;51(9):1610–7. 10.1093/rheumatology/kes078.
Aletaha D, Smolen JS. Joint damage in rheumatoid arthritis progresses in remission according to the disease activity score in 28 joint and is driven by residual swollen joints. Arthritis Rheum. 2011;63(12):3702–11. 10.1002/art.30634. DOI: 10.1002/art.30634
Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, et al. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission. Evidence from an imaging study may explain structural progression. Arthritis Rheum. 2006;54(12):3761–73. 10.1002/art.22190.
Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl L, Funovits J, et al. American College of Rheumatology/European league against rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011;63(3):573–86. 10.1002/art.30129.
Saleem B, Brown AK, Keen H, Nizam S, Freeston J, Wakefield R, et al. Should imaging be a component of rheumatoid arthritis remission criteria? A comparison between traditional and modified composite remission scores and imaging assessments. Ann Rheum Dis. 2011;70(5):792–8. 10.1136/ard.2010.134445.
Zufferey P, Möller B, Brulhart L, Tamborrini G, Scherer A, Finckh A, et al. Persistence of ultrasound synovitis in patients with rheumatoid arthritis fulfilling the DAS28 and/or the new ACR/EULAR RA remission definitions: results of an observational cohort study. Joint Bone Spine. 2014;81(5):426–32. 10.1016/j.jbspin.2014.04.014.
Horton SC, Tan AL, Freeston JE, Wakefield RJ, Buch MH, Emery P. Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: implications for the use of ultrasound within a treatment-to-target strategy. Rheumatology. 2016;55(7):1177–87. 10.1093/rheumatology/kew037. DOI: 10.1093/rheumatology/kew037
Nguyen H, Ruyssen-Witrand A, Gandjbakhch F, Constantin A, Foltz V, Cantagrel A. Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis. Rheumatology. 2014;53(11):2110–8. 10.1093/rheumatology/keu217. DOI: 10.1093/rheumatology/keu217
Sewerin P, Vordenbaeumen S, Hoyer A, et al. Silent progression in patients with rheumatoid arthritis: is DAS28 remission an insufficient goal in RA? Results from the German Remission-plus cohort. BMC Musculoslelet Disord. 2017;18:163. DOI: 10.1186/s12891-017-1528-y
Conaghan PG, O’Connor P, McGonagle D, et al. Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Arthritis Rheum. 2003;48(1):64–71. 10.1002/art.10747. DOI: 10.1002/art.10747
Brown AK, Conaghan PG, Karim Z, Quinn MA, Ikeda K, Peterfy CG, et al. An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum. 2008;58(10):2958–67. 10.1002/art.23945.
Foltz V, Gandjbakhch F, Etchepare F, Rosenberg C, Tanguy ML, Rozenberg S, et al. Power Doppler ultrasound, but not low-field magnetic resonance imaging, predicts relapse and radiographic disease progression in rheumatoid arthritis patients with low level of disease activity. Arthritis Rheum. 2012;64(1):67–76. 10.1002/art.33312.
Scirè CA, Montecucco C, Codullo V, et al. Ultrasonographic evaluation of joint involvement in early rheumatoid arthritis in clinical remission: power Doppler signal predicts short-term relapse. Rheumatology. 2009;48(9):1092–7. 10.1093/rheumatology/kep171. DOI: 10.1093/rheumatology/kep171
Haavardsholm EAN, Aga AB, Olsen IC, et al. Ultrasound in management of rheumatoid arthritis: ARTIC randomised controlled strategy trial. Br Med J. 2016;354:i4205. DOI: 10.1136/bmj.i4205
Polisson RP, Schoenberg OI, Fischman A, Rubin R, Simon LS, Rosenthal D, et al. Use of magnetic resonance imaging and positron emission tomography in the assessment of synovial volume and glucose metabolism in patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(6):819–25. 10.1002/art.1780380616.
Palmer WE, Rosenthal DI, Schoenberg OI, Fischman AJ, Simon LS, Rubin RH, et al. Quantification of inflammation in the wrist with gadolinium-enhanced MR imaging and PET with 2-[F−18]-fluoro-2-deoxy-D-glucose. Radiology. 1995;196(3):647–55. 10.1148/radiology.196.3.7644624.
Elzinga EH, van der Laken CJ, Comans EFI, Lammertsma AA, Dijkmans BAC, Voskuyl AE. 2-Deoxy-2[F-18] fluoro-D-glucose joint uptake on positron emission tomography images: rheumatoid arthritis versus osteoarthritis. Mol Imaging Biol. 2007;9(6):357–60. 10.1007/s11307-007-0113-4. DOI: 10.1007/s11307-007-0113-4
Elzinga EH, van der Laken CJ, Comans EFI, Boellaard R, Hoekstra OS, Dijkmans BAC, et al.18F-FDG PET as a tool to predict the clinical outcome of infliximab treatment of rheumatoid arthritis: an explorative study. J Nucl Med. 2011;52(1):77–80. https://doi.org/10.2967/jnumed.110.076711.
Roivainen A, Hautaniemi S, Möttönen T, Nuutila P, Oikonen V, Parkkola R, et al. Correlation of18F-FDG PET/CT assessments with disease activity and markers of inflammation in patients with early rheumatoid arthritis following the initiation of combination therapy with triple oral antirheumatic drugs. Eur J Nucl Med Mol Imaging. 2013;40(3):403–10. https://doi.org/10.1007/s00259-012-2282-x.
Beckers C, Ribbens C, André B, Marcelis S, Kaye O, Mathy L, et al. Assessment of disease activity in rheumatoid arthritis with18F-FDG PET. J Nucl Med. 2004;45(6):956–64.
Beckers C, Jeukens X, Ribbens C, André B, Marcelis S, Leclercq P, et al.18F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3. Eur J Nucl Med Mol Imaging. 2006;33(3):275–80. https://doi.org/10.1007/s00259-005-1952-3.
Lee SJ, Jeong JH, Lee CH, et al. Development and validation of an 18F-fluorodeoxyglucose-positron emission tomography with computed tomography-based tool for the evaluation of joint counts and disease activity in patients with rheumatoid arthritis. Arthritis Rheum. 2019;71:1232–40. DOI: 10.1002/art.40860
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81. 10.1002/art.27584.
Fries JF, Spitz PW, Young DY. The dimension of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol. 1982;9(5):789–93.
Inoue E, Yamanaka H, Hara M, Tomatsu T, Kamatani N. Comparison of disease activity score (DAS)28-erythrocyte sedimentation rate and DAS28-C-reactive protein threshold values. Ann Rheum Dis. 2007;66(3):407–9. 10.1136/ard.2006.054205. DOI: 10.1136/ard.2006.054205
Aletaha D, Nell VPK, Stamm T, Uffmann M, Pflugbeil S, Machold K, et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther. 2005;7(4):R796–806. https://doi.org/10.1186/ar1740.
Boyesen P, Machado P. Measuring disease activity and damage in arthritis. In: Bijlsma JWJ, Hachulla E, editors. Textbook on rheumatic diseases. London: BMJ Publishing Group Ltd; 2015. p. 1223–55.
Liu Y, Ghesani NV, Zuckier LS. Physiology and pathophysiology of incidental findings detected on FDG-PET scintigraphy. Semin Nucl Med. 2010;40(4):294–315. 10.1053/j.semnuclmed.2010.02.002. DOI: 10.1053/j.semnuclmed.2010.02.002
Miese F, Scherer A. OStendorf et al. hybrid 18F-FDG PET-MRI of the hand in theumatoid arthritis: initial results. Clin Rheumatol. 2011;30(9):1247–50. 10.1007/s10067-011-1777-3. DOI: 10.1007/s10067-011-1777-3